Taper Or Abrupt Steroid Stop: TOASSTtrial

Phase 4

Recruiting

• Conditions: Inflammatory Disorder; Autoimmune
• Interventions: Other: Placebo Arm; Drug: Prednisone

• Registration Number: NCT03153527
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

This study is an Investigator-initiated, placebo-controlled, multicenter noninferiority trial, comparing rapid termination of systemic glucocorticoid treatment with a tapering regime over 4 weeks.

Detailed Description

In total, 573 patients will be enrolled. Patients will be randomly assigned in a 1:1 ratio to either prednisone in decreasing doses over 4 weeks or placebo.

Patients, treating physicians, and study personnel will be blinded to treatment allocation to either prednisone or matching placebo. At inclusion, we will perform a 250 micrograms Synacthen® stimulation test. The results of the test will be blinded to treating physicians and investigators, and its value to predict clinical outcome will only be assessed after completion of the trial. As a safety measure, all patients will be instructed about stress coverage as well as signs and symptoms of hypocortisolism and will be provided with emergency medication. Patients will be randomized to the standard (tapering) or the experimental (matching placebo) arm. Follow-up will be for six months. In order to improve adherence to the study and ensure feasibility, follow-up visits in most study centers will be by telephone only. Visits will be performed early after stopping glucocorticoids in both arms (i.e. at days 7 and 35) to ensure safety; the other two visits will be on days 90 and 180.

Amendment approved in 1-2018: former exclusion criterion 'status post organ transplantation' was revised and deleted

Study Timeline

• Study First Submitted: 2017-05-05
• Study First Submitted QC: 2017-05-11
• Study First Posted: 2017-05-15
• Study Start: 2017-05-31
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-22
• Last Update Posted: 2023-11-24
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 573

Inclusion Criteria

• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Age ≥ 18 years
• Daily glucocorticoid dose ≥ 7.5 mg prednisone-equivalent at the time of inclusion
• Therapy over ≥ 28 days, ≥ 7.5 mg average daily dose, with a cumulative glucocorticoid dose ≥ 420 mg prednisone-equivalent prior to inclusion
• Tapering not or no longer mandatory to treat underlying disease

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Exclusion Criteria

• Primary adrenal failure
• Treatment with systemic depot glucocorticoids (e.g. intramuscular, epidural)
• Incapability to administer glucocorticoid cover treatment in situations of stress
• Inability or unwillingness to provide informed consent
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
• Known or suspected non-compliance
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo arm (intervention arm)	Placebo Arm	Stop glucocorticoid treatment; administer placebo matching the verum preparation in weekly intervals.
Verum group (control/standard arm)	Prednisone	If patient is on \> 7.5 mg prednisone-equivalent daily: administer 7.5 mg q.d. for 7 days, then 5 mg q.d. for 7 days, then 2.5 mg q.d. for 7 days, then 2.5 mg q.d. every second day, then stop. If patient on 7.5 mg q.d.: maintain for 7 days, then taper as above.

Primary Outcome Measures

Name	Time	Method
Time to any incidence	up to 6 months	Time to first occurrence of hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis (defined as glucocorticoid-responsive hypotension or shock with or without accompanying symptoms and signs such as weakness, apathy, nausea, vomiting, abdominal pain, hypothermia, hyponatremia \[serum sodium \< 135 millimole (mM)\], hyperkalemia \[serum potassium \> 5 mM\], hypoglycemia \[plasma glucose \< 3.5 mM\]); whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure	up to 6 months	Cumulative systemic glucocorticoid dose administered to treat or prevent adrenal failure
Cumulative overall systemic glucocorticoid dose	up to 6 months	Cumulative overall systemic glucocorticoid dose
General health status	assessed at days 1, 7, 28, 35, 90,180	General health status as self-assessed by the participant on a visual analog scale (VAS) from 0 to 100
Score of symptoms and signs of hypocortisolism	up to 6 months	Score of symptoms and signs of hypocortisolism: weakness, hypothermia, nausea, vomiting, abdominal pain, fatigue, dizziness, Blood pressure, serum Na and serum glucose concentrations.
Time to specific incidence	up to 6 months	Time to first occurrence of individual components of the primary outcome;
Cumulative systemic glucocorticoid dose administered to treat relapse	up to 6 months	Cumulative systemic glucocorticoid dose administered to treat relapse of disease, specified for each disease
Performance in 250 mcg Synacthen® test	up to 6 months	Performance in 250 mcg Synacthen® test: test assessed day 1 in all participants, plus days 7 and 35 in those followed in centers Bruderholz, Luzern, Aarau
In patients hospitalized at study entry: length of hospital stay	up to 6 months	In patients hospitalized at study entry: length of hospital stay

Trial Locations

Locations (15)

Stoffwechselzentrum, Kantonsspital Olten; 🇨🇭 Olten, Switzerland

Department of Internal Medicine, Kantonsspital St. Gallen; 🇨🇭 St. Gallen, Switzerland

Departement of Internal Medicine, Kantonsspital Aarau; 🇨🇭 Aarau, Switzerland

University Hospital Frankfurt; 🇩🇪 Frankfurt, Germany

Endocrinology/Diabetology/Metabolism; University Hospital Basel; 🇨🇭 Basel, Switzerland

Geneva University Hospitals; 🇨🇭 Geneva, Switzerland

Department of Internal Medicine, Kantonsspital Münsterlingen; 🇨🇭 Münsterlingen, Switzerland

University Hospital Würzburg; 🇩🇪 Würzburg, Germany

Division of Gastroenterology, Spital Bülach AG; 🇨🇭 Bülach, Switzerland

Kantonsspital Baden; 🇨🇭 Baden, Switzerland

Department of Rheumatology, Immunology, and Allergology, Inselspital; 🇨🇭 Bern, Switzerland

Dept. of Endocrinology, Diabetology and Clinical Nutrition, University Hospital; 🇨🇭 Zürich, Switzerland

Kantonsspital Frauenfeld; 🇨🇭 Frauenfeld, Switzerland

Center for Primary Health Care,University of Basel, Kantonsspital Baselland; 🇨🇭 Liestal, Switzerland

Internal Medicine, Kantonsspital Baselland/Liestal; 🇨🇭 Liestal, Switzerland